The effects of streptozotocin on rates of glucose utilization, oxidation, and production in the sheep fetus

Abstract

Streptozotocin was injected into chronically catheterized, late gestation fetal sheep to produce hypoinsulinemia and to investigate the effects of hypoinsulinemia on the rates of utilization and production of glucose. Each fetus received two IV doses of streptozotocin (100 mg/kg estimated fetal weight per dose). Experiments were conducted before and five to six days after giving the streptozotocin. Experiments consisted of direct measurement of fetal glucose utilization rate (using [U- 14C]glucose tracer) and umbilical glucose uptake rate (Fick principle) during basal and glucose infusion periods. Fetal endogenous production rate was calculated as the difference between rates of fetal glucose utilization and umbilical glucose uptake. Following streptozotocin injections the rate of fetal glucose utilization was reduced (5.50 ± 0.34 to 4.13 ± 0.32 mg/kg/min) as was the rate of fetal CO 2 production from fetal glucose carbon oxidation (91.7 ± 5.3 to 71.7 ± 6.0 μmol/kg/min) and the rate of fetal glucose oxidation (2.75 ± 0.16 to 2.15 ± 0.18 mg/kg/min). At the same time the rate of fetal endogenous glucose production was enhanced (0.31 ± 0.18 to 2.06 ± 0.28 mg/kg/min). These changes in glucose metabolism were accompanied by hypoinsulinemia (16 ± 2 to 8 ± 1 μU/mL), an inhibition of insulin secretion in response to glucose infusion (16 ± 2 to 34 ± 2 μU/mL control, 8 ± 1 to 9 ± 1 μU/mL after streptozotocin), hyperglycemia (19.5 ± 0.7 to 30.4 ± 1.7 mg/dL), and a reduction in the rate of umbilical glucose uptake (5.19 ± 0.34 to 2.07 ± 0.40 mg/kg/min). The disturbances in glucose metabolism could be alleviated only in part by insulin infusion. These observations show that streptozotocin administration to late gestation fetal sheep changes most aspects of fetal glucose metabolism and indicate that not all the changes may be attributed to hypoinsulinemia per se.